Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal alanine aminotransferase and high serum HBV DNA levels

Örmeci, Aslı; Aydın, Yücel; Şumnu, Abdullah; Baran, Bülent; Soyer, Özlem Mutluay; Pınarbaşı, Binnur; Göktürk, Suut; Güllüoğlu, Mine; Önel, Derya; Badur, Selim; Akyüz, Filiz; Karaca, Çetin; Demır, Kadir; Beşışık, Fatih; Kaymakoğlu, Sabahattin

doi:10.1016/j.ijid.2016.09.007

Cited by 21 publications

(32 citation statements)

References 23 publications

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“…When the studies carried out in Shanghai and Zhejiang are directly compared, the population of PNALT patients with an HAI score ranging from 4 to 6 is increasing. The situation in China aligns with observations in other Asian countries [24–26], in which 35% of PNALT patients with mild and moderate necroinflammation were observed.…”

Section: Discussionsupporting

confidence: 86%

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China

Xing

Zhou

et al. 2018

PLoS ONE

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BackgroundThe aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy.MethodsLiver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak’s fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out.ResultsOf the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30–39, 40–49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3).ConclusionOur results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.

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Section: Discussionsupporting

confidence: 86%

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China

Xing

Zhou

et al. 2018

PLoS ONE

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“…Treatment requirement was observed in 40% of the patients in total according to histology. These two differences in comparison with our study may be related with the fact that only patients with normal ALT levels were included in the study of Ormeci …”

Section: Discussioncontrasting

confidence: 56%

“…In the study conducted by Örmeci et al from our country, HBeAg negative patients who underwent liver biopsy with a HBV DNA value of 2000 IU/mL and persistently normal ALT levels were included. The same criterion was used for significant liver injury (HAI ≥6 and/or stage ≥2 by Ishak's classification) as in our study.…”

Section: Discussionmentioning

confidence: 99%

Predictors of histological indication for treatment in HBeAg negative chronic HBV infection

et al. 2017

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In this study, we evaluated the relationship of hepatitis B virus (HBV) DNA levels with liver histology and various other liver related parameters and the predictors of histologically active liver disease requiring treatment (Histological activity ≥6 and/or grade ≥2 by Ishak's classification) in patients with HBeAg negative chronic HBV infection. Demographic data, laboratory findings and liver histology findings of patients with no clinical cirrhosis who underwent liver biopsy considering HBeAg negative chronic hepatitis (HBV DNA >2000 IU/mL) were analyzed. Two hundred and fifteen patients were included in this retrospective study. Treatment indication by histologic findings were 85.7%, 61.2%, and 64%, respectively, in group 1 (HBV DNA ≥200 000), group 2 (HBV DNA 20 000-200 000), and group 3 (HBV DNA 2000-20 000 IU/mL) (P = 0.001). Group 1 was different from other groups in terms of aspartate aminotransferase (AST), alanine aminotransferase (ALT), fibrosis stage, necroinflammatory activity, and platelet count. Multiple logistic regression analysis revealed that, advanced age (cut-off was 46 years), higher than normal AST and HBV DNA ≥200 000 IU/mL (compared to group 3) were found to be the predictors of histologically active disease with treatment indication. Conclusively, most of the patients with HBV DNA ≥200 000 IU/mL showed treatment requiring liver injury, but also a significant portion of the patients with HBV DNA 2000-200 000 IU/mL carried an indication for treatment. Although age (>46 years) and AST (>40 IU/L) can be helpful to predict treatment requirement in patients with HBV DNA 2000-200 000 IU/mL, sufficient effort should be made to find out the significant liver damage.

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“… 48 Moreover, in patients with normal serum ALT and levels of HBV DNA between 2000 and 20 000 IU/mL (so-called grey-zone patients), significant levels of fibrosis have been reported. 49 We have previously shown that patients considered ‘immune tolerant’ (HBeAg+chronic infection) had levels of fibrosis similar to those found in patients labelled immune active (HBeAg±chronic hepatitis), notwithstanding differences in biochemical and virological parameters. 50 …”

Section: What We Are Missing In the Bloodmentioning

confidence: 64%

Liver sampling: a vital window into HBV pathogenesis on the path to functional cure

Gill

Pallett²,

Kennedy

et al. 2018

Gut

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In order to optimally refine the multiple emerging drug targets for hepatitis B virus (HBV), it is vital to evaluate virological and immunological changes at the site of infection. Traditionally liver biopsy has been the mainstay of HBV disease assessment, but with the emergence of non-invasive markers of liver fibrosis, there has been a move away from tissue sampling. Here we argue that liver biopsy remains an important tool, not only for the clinical assessment of HBV but also for research progress and evaluation of novel agents. The importance of liver sampling has been underscored by recent findings of specialised subsets of tissue-resident immune subsets capable of efficient pathogen surveillance, compartmentalised in the liver and not sampled in the blood. Importantly, the assessment of virological parameters, such as cccDNA quantitation, also requires access to liver tissue. We discuss strategies to maximise information obtained from the site of infection and disease pathology. Fine needle aspirates of the liver may allow longitudinal sampling of the local virus/host landscape. The careful utilisation of liver tissue and aspirates in conjunction with blood will provide critical information in the assessment of new therapeutics for the functional cure of HBV.

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Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal alanine aminotransferase and high serum HBV DNA levels

Abstract: Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years.

Cited by 21 publications

References 23 publications

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China

Predictors of histological indication for treatment in HBeAg negative chronic HBV infection

Liver sampling: a vital window into HBV pathogenesis on the path to functional cure

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